<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Spontaneous delivery represents an important way triggering the physiological mechanisms essential for a proper postnatal adaptation of a newborn. Autonomic nervous system (ANS) plays a crucial role in this process. There is insufficient data concerning the impact of different delivery mode on ANS in newborns. Therefore, we aimed to study the effect of delivery mode on sympathetic nervous system (SNS) in healthy term newborns measured by electrodermal activity (EDA).</p>
</sec>
<sec><h3>Material &amp; Methods</h3>
<p>The study conducted 50 healthy full – term newborns divided into two groups: the spontaneous delivery group (SD, n=27) and the caesarean section group (CS, n=23). EDA parameters (SCL – tonic level of skin conductance; NS.SCRs – non – specific phasic responses of skin conductance) were evaluated during three measurements: 2<sup>nd</sup> (M1), 24<sup>th</sup> (M2), and 72<sup>nd</sup> (M3) hours of life.</p>
</sec>
<sec><h3>Results</h3>
<p>SCL significantly decreased during the first day of life (M1 vs. M2 – p &lt; 0.001). The lowest NS.SCRs values were demonstrated in M1 in both groups with significant differences in CS group between measurements – M1 vs. M2 (p=0.001) and M1 vs. M3 (p=0.005). However, a significantly lower NS.SCRs was found in CS group (p=0.01) early after birth (M1).</p>
</sec>
<sec><h3>Conclusion</h3>
<p>Our findings revealed a reduced NS.SCRs indicating potential decreased „arousal“ in CS group – it seems that the attenuated „arousal“ could reflect the absence of physiological labor mechanisms as well as the effect of anesthesia leading to discrete early functional abnormalities in CS group. Further research is needed to validate these findings.</p>
</sec>
</abstract>

Background
Spontaneous delivery represents an important way triggering the physiological mechanisms essential for a proper postnatal adaptation of a newborn. Autonomic nervous system (ANS) plays a crucial role in this process. There is insufficient data concerning the impact of different delivery mode on ANS in newborns. Therefore, we aimed to study the effect of delivery mode on sympathetic nervous system (SNS) in healthy term newborns measured by electrodermal activity (EDA).

Material & Methods
The study conducted 50 healthy full – term newborns divided into two groups: the spontaneous delivery group (SD, n=27) and the caesarean section group (CS, n=23). EDA parameters (SCL – tonic level of skin conductance; NS.SCRs – non – specific phasic responses of skin conductance) were evaluated during three measurements: 2nd (M1), 24th (M2), and 72nd (M3) hours of life.

Results
SCL significantly decreased during the first day of life (M1 vs. M2 – p < 0.001). The lowest NS.SCRs values were demonstrated in M1 in both groups with significant differences in CS group between measurements – M1 vs. M2 (p=0.001) and M1 vs. M3 (p=0.005). However, a significantly lower NS.SCRs was found in CS group (p=0.01) early after birth (M1).

Conclusion
Our findings revealed a reduced NS.SCRs indicating potential decreased „arousal“ in CS group – it seems that the attenuated „arousal“ could reflect the absence of physiological labor mechanisms as well as the effect of anesthesia leading to discrete early functional abnormalities in CS group. Further research is needed to validate these findings.


<div xmlns="http://www.w3.org/1999/xhtml">
<sec id="j_acm-2023-0010_s_001"><div>INTRODUCTION</div>
<p>Spontaneous delivery (SD) is a natural way of human birth. From the physiological aspect, SD represents a crucial stress trigger, which is the substantial premise for a normal postnatal adaptation of a newborn. Several mechanisms participate on the triggering of perinatal stress – the onset of labor, change of environment (in utero to ex utero) with the mechanical (e.g. pressure of the birth canal) and temperature (and many other) stimuli affecting the neonatal organism during peripartal period (<a ref-type="bibr" href="#j_acm-2023-0010_ref_001">1</a>). All these factors result into the activation of sympathetic nervous system (SNS) together with an increased production of catecholamine and cortisol in neonate (<a ref-type="bibr" href="#j_acm-2023-0010_ref_002">2</a>). This is very important for the extrauterine adaptation of the respiratory and circulatory systems, thermogenesis, and energy metabolism (<a ref-type="bibr" href="#j_acm-2023-0010_ref_001">1</a>). The labor without associated neonatal stress (i.e. elective caesarean section) is a potential factor which interferes in the process of postnatal adaptation (<a ref-type="bibr" href="#j_acm-2023-0010_ref_003">3</a>).</p>
<p>The autonomic nervous system (ANS), consisting of SNS and parasympathetic nervous system (PNS), is extremely important for postnatal adaptation in newborns. More specifically, SNS enables brisk adaptation to postnatal life (<a ref-type="bibr" href="#j_acm-2023-0010_ref_002">2</a>). From the developmental aspect, SNS is characterized by steady maturation during the pregnancy and requires at least 37 gestational weeks to reach accurate functioning (<a ref-type="bibr" href="#j_acm-2023-0010_ref_004">4</a>). Maturation of ANS also continues after birth with PNS predominance in term neonates (<a ref-type="bibr" href="#j_acm-2023-0010_ref_005">5</a>).</p>
<p>Electrodermal activity (EDA) also known as skin conductance (SC) represents a useful parameter reflecting the changes exclusively in SNS (<a ref-type="bibr" href="#j_acm-2023-0010_ref_006">6</a>). The measurement of EDA reflects the changes of the skin electrical conductivity due to the activity of eccrine sweat glands. This phenomenon is under the pure control of sympathetic cholinergic nervous system (<a ref-type="bibr" href="#j_acm-2023-0010_ref_007">7</a>). Peripheral SNS together with sweat glands located in the palms and plants are developed in the second trimester of pregnancy and continue to mature (<a ref-type="bibr" href="#j_acm-2023-0010_ref_008">8</a>). In term newborns, fully developed functional emotional sweating was reported (<a ref-type="bibr" href="#j_acm-2023-0010_ref_009">9</a>). From this perspective, EDA method represents an optimal tool for the assessment of SNS function in term newborns. In addition, EDA measurement is a safe, non – invasive, easy to handle method only little influenced by other factors (e.g. circulatory changes).</p>
<p>Understanding of normal early postnatal ANS function in full – term healthy newborns may provide a useful reference for studies of high – risk neonates and may have a prognostic value. Therefore, it is important to elucidate how different delivery modes influence the measures of ANS function in low – risk term newborns (<a ref-type="bibr" href="#j_acm-2023-0010_ref_010">10</a>). To the best of our knowledge, there are no studies concerning the influence of delivery mode on SNS function and maturation measured by EDA within the first postnatal days in healthy term neonates. Therefore, we aimed to study potential changes in SNS indexed by EDA in early postnatal adaptation period in newborns depending on the delivery mode.</p>
</sec>
<sec id="j_acm-2023-0010_s_002"><div>MATERIALS AND METHODS</div>
<sec id="j_acm-2023-0010_s_002_s_001"><div>Subjects</div>
<p>Our study was conducted from January 2019 to February 2020 at the Clinic of Neonatology of the University Hospital and Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava. The study included 50 healthy eutrophic full – term newborns with physiological immediate postnatal adaptation (Apgar score ≥ 8 points in the 1st minute and ≥ 9 in the 5th and 10th minute) who were divided into 2 groups according to the delivery mode: the spontaneous delivery (SD) group and the caesarean section (CS) group. All women who underwent caesarean section were in general anesthesia (a combination of intravenous thiopental and the inhaled sevofluran). Only newborns with indications of elective caesarean section were included (breech presentation, repeat caesarean section, primary maternal indication for caesarean section). SD group consisted of babies without the need for instrumental delivery (i.e., forceps and vacuum extractor).</p>
<p>Exclusion criteria involved all conditions that are proven or very likely associated with abnormal ANS function: pathological gravidity (preterm delivery, intrauterine growth restriction, etc.), maternal systemic disease (gestational or another types of diabetes), smoking during pregnancy, congenital anomaly of the neonate, signs of perinatal infection, metabolic disorders: hypoglycaemia and hyperbilirubinemia requiring phototherapy during hospitalization.</p>
</sec>
<sec id="j_acm-2023-0010_s_002_s_002"><div>Measurement and data analysis</div>
<p>The examination was performed during the day (7 am – 12 am) and during sleep or quiet alert state in the supine position under standard conditions with the minimization of internal and external stimuli. Two silver – silver chloride bipolar electrodes with a sampling rate of 256 Hz placed on the sole of the neonate were used for the continuous EDA recording (FlexComp Infinity Biofeedback, Thought Technology Ltd., Canada) according to the recommendation of EDA biosignal measurements (<a ref-type="bibr" href="#j_acm-2023-0010_ref_011">11</a>). The examination protocol included three EDA measurements that were performed 2 hours (measurement 1 – M1), 24 hours (measurement 2 – M2), and 72 hours (measurement 3 – M3) after birth. After the stabilization of the subjects (approximately 10 minutes – adaptation interval) the measurement of EDA was initiated (6 minutes records). EDA raw records were checked and the artefacts were removed for the final data analysis. The tonic EDA component was extracted by the 10<sup>th</sup> order low – pass finite impulse response filter (<a ref-type="bibr" href="#j_acm-2023-0010_ref_012">12</a>). The following EDA parameters were analyzed: 1) <italic>skin conductance level</italic> (SCL, microSiemens (μS)) – an index of tonic level of skin electrical conductivity; 2) <italic>non – specific skin conductance responses</italic> (NS.SCRs) – reflecting momentary <italic>“arousal”</italic> with fixed threshold (0.05 μS – evaluated as a rate of spontaneous skin conductance response waves without external stimuli) (<a ref-type="bibr" href="#j_acm-2023-0010_ref_013">13</a>).</p>
</sec>
<sec id="j_acm-2023-0010_s_002_s_003"><div>Statistical analysis</div>
<p>Jamovi version 1.6.9 (Sydney, Australia) was used for the statistical analysis and visualization of the measured data. The distribution and normality of the data was assessed using a violin plot and the Shapiro – Wilk normality test. Because of non – normal data distribution, the non – parametric ANOVA (Friedman test with post hoc Durbin – Conover test) was used. A value of p &lt; 0.05 (two – tailed) was considered statistically significant.</p>
</sec>
<sec id="j_acm-2023-0010_s_002_s_004"><div>Ethical approval</div>
<p>This paper presents the preliminary data of our prospective observational study „Assessment of Autonomic Nervous Regulation During Postnatal Period in Newborns“ registered in Clinical Trials (ID NCT03830424). The clinical study was approved by the Ethics Committee of the Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava (EK 69/2018). All procedures performed in the study were in accordance with the 2000 Helsinki declaration of the World Medical Association. The subjects were included after meeting the inclusion criteria and with an approval by their parents after signing the informed consent.</p>
</sec>
</sec>
<sec id="j_acm-2023-0010_s_003"><div>RESULTS</div>
<p>Our set of subjects consists of 50 newborns (28 girls, mean gestational age 39 ± 0.21 weeks, mean birthweight 3362 ± 79 grams). Baseline characteristics of subject groups according to delivery mode is presented in <a ref-type="table" href="#j_acm-2023-0010_tab_001">Table 1</a>.</p>
<table-wrap id="j_acm-2023-0010_tab_001" position="float"><label>Table 1</label>
<caption><p>Baseline characteristics of subject groups</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th align="left" valign="middle" colspan="4">DELIVERY MODE</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top"></td>
<td align="left" valign="top">SD</td>
<td align="left" valign="top">CS</td>
<td align="left" valign="top">p</td>
</tr>
<tr>
<td align="left" valign="top">N (girls)</td>
<td align="left" valign="top">27 (17)</td>
<td align="left" valign="top">23 (12)</td>
<td align="left" valign="top">–</td>
</tr>
<tr>
<td align="left" valign="top">GA (weeks)</td>
<td align="left" valign="top">39.4 ± 0.23</td>
<td align="left" valign="top">38.4 ± 0.34</td>
<td align="left" valign="top"><italic>0.017</italic></td>
</tr>
<tr>
<td align="left" valign="top">BW (g)</td>
<td align="left" valign="top">3383 ± 113</td>
<td align="left" valign="top">3335 ± 110</td>
<td align="left" valign="top">0.685</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn-group>
<fn><p>BW = birthweight, CS = caesarean section, GA = gestational age, N = number of subjects, SD = spontaneous delivery</p></fn>
</fn-group>
</table-wrap-foot>
</table-wrap>
<sec id="j_acm-2023-0010_s_003_s_001"><div>Intragroup comparison</div>
<p>Non – parametric Friedman test showed a significant effect of delivery mode for the parameters NS.SCRs (F[1]=6.66; p=0.01) and a mixed effect of mode of delivery and phase for the parameters SCL (F[5]=42.0; p &lt;0.001), NS.SCRs (F[5]=25.9; p&lt;0.001). Post – hoc analysis revealed a significantly higher SCL in M1 vs M2 (SD: p&lt;0.001; CS: p&lt;0.001) and M1 vs M3 (SD: p=0.003; CS: p=0.028) in both groups. However, a significant difference in NS.SCRs was observed only in CS: significantly lower values in M1 vs M2 (p=0.001) and M1 vs M3 (p=0.005) (<a ref-type="fig" href="#j_acm-2023-0010_fig_001">Fig 1</a>). There was no difference in the remaining parameters.</p>
<figure id="j_acm-2023-0010_fig_001" position="float" fig-type="figure"><h2>Fig. 1</h2>
<figCaption><p>Changes of EDA parameters within first three postnatal days according to the delivery mode.</p><p>A) SCL – skin conductance level; B) NS.SCRs – nonspecific skin conductance responses. CS = caesarean section; SD = spontaneous delivery, μS = microsiemens. Values are present as a mean ± standard error of the mean (SEM). Symbols: * = significant difference between the measurements in SD group; # = significant difference between the measurements in CS group; symbols above „24 hours“ represent the difference between M1 and M2; symbols above „72 hours“ represent the difference between M1 and M3; *, <sup>#</sup> p &lt; 0.05; **, <sup>##</sup> p &lt; 0.01; ***, <sup>###</sup> p &lt; 0.001.</p></figCaption>
<img xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_acm-2023-0010_fig_001.jpg" src="https://sciendo-parsed.s3.eu-central-1.amazonaws.com/64e12b6266cae56d9e7abac8/j_acm-2023-0010_fig_001.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20240621T142353Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=18000&amp;X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240621%2Feu-central-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=b1f23c8b1f7d27e9579158444b192bdbbb08cd6eeb80627422eecfd7e6d42ed9" class="mw-100"/>
</figure>
</sec>
<sec id="j_acm-2023-0010_s_003_s_002"><div>Intergroup comparison</div>
<p>The statistical analysis revealed a significantly lower NS.SCRs in neonates born by CS vs SD in M1 (p=0.01). (<a ref-type="table" href="#j_acm-2023-0010_tab_002">Table 2</a>). No significant differences were revealed in the remaining parameters.</p>
<table-wrap id="j_acm-2023-0010_tab_002" position="float"><label>Table 2</label>
<caption><p>Comparison of EDA parameters between groups</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th align="left" valign="middle" rowspan="2"></th>
<th align="center" valign="middle" colspan="2">M1 <sup>a</sup></th>
<th align="center" valign="middle" colspan="2">M2 <sup>b</sup></th>
<th align="center" valign="middle" colspan="2">M3 <sup>c</sup></th>
<th align="center" valign="middle" rowspan="2">p <sup>a</sup></th>
<th align="center" valign="middle" rowspan="2">p <sup>b</sup></th>
<th align="center" valign="middle" rowspan="2">p <sup>c</sup></th>
</tr>
<tr>
<th align="center" valign="middle">SD (n=27)</th>
<th align="center" valign="middle">CS (n=23)</th>
<th align="center" valign="middle">SD (n=27)</th>
<th align="center" valign="middle">CS (n=23)</th>
<th align="center" valign="middle">SD (n=27)</th>
<th align="center" valign="middle">CS (n=23)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">SCL (μS)</td>
<td align="center" valign="top">3.74±0.68</td>
<td align="center" valign="top">2.96±0.62</td>
<td align="center" valign="top">0.49±0.15</td>
<td align="center" valign="top">0.33±0.12</td>
<td align="center" valign="top">1.40±0.30</td>
<td align="center" valign="top">0.87±0.30</td>
<td align="center" valign="top">0.461</td>
<td align="center" valign="top">0.54</td>
<td align="center" valign="top">0.964</td>
</tr>
<tr>
<td align="left" valign="top">NS.SCRs(/min)</td>
<td align="center" valign="top">3.58±1.35</td>
<td align="center" valign="top">1.46±0.74</td>
<td align="center" valign="top">5.54±0.79</td>
<td align="center" valign="top">5.26±1.13</td>
<td align="center" valign="top">5.00±1.33</td>
<td align="center" valign="top">4.96±1.35</td>
<td align="center" valign="top"><italic>0.01</italic></td>
<td align="center" valign="top">0.457</td>
<td align="center" valign="top">0.597</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn-group>
<fn><p>SCL – skin conductance level; NS.SCRs – nonspecific skin conductance responses. CS = caesarean section; SD = spontaneous delivery; μS = microsiemens; p = statistical significance; n = number of subjects; M1 = 1<sup>st</sup> measurement; M2 = 2<sup>nd</sup> measurement; M1 = 3<sup>rd</sup> measurement</p></fn>
</fn-group>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="j_acm-2023-0010_s_004"><div>DISCUSSION</div>
<p>Our study investigated the potential effect of delivery mode on SNS activity and maturation during early postnatal life in healthy term neonates evaluated by EDA analysis. The major findings of this study are following: 1) significantly higher values of SCL were observed early after birth (M1) in all newborns followed by a significant decrease during the following measurements (M2 and M3) reflecting a post – delivery stress – related sympathetic withdrawal after postnatal adaptation; 2) NS.SCRs representing the <italic>„arousal“</italic> phenomenon was lower in all subjects early after birth (M1) compared to the following measurements (M2 and M3). The increase within 24 hours of life may reflect changes related to an increased sensory processing and receptor activation related to the adaptation to the environment; 3) NS.SCRs was significantly lower in CS group reflecting the effect of delivery mechanism and peripartal general anesthesia administered to the mothers undergoing CS. Based on our results we suggest that EDA measurement may represents a sensitive tool to determine the developmental and maturational changes in SNS during the earliest postnatal life. Several mechanisms are supposed:</p>
<p>During the peripartal period, the SNS outflow from central ANS structures increases and together with neuroendocrine support (e.g. catecholamines) enables brisk postnatal adaptation (<a ref-type="bibr" href="#j_acm-2023-0010_ref_002">2</a>). After birth, SNS constantly continues to develop. Regarding the development and normal functioning of palmar and plantar sweat glands, Harpin and Rutter (<a ref-type="bibr" href="#j_acm-2023-0010_ref_009">9</a>) reported functional emotional sweating in term neonates. Our study showed the highest values of SCL in all newborns 2 hours after birth supporting the functionality of eccrine sweat glands in term neonates immediately after delivery. According to our results, SNS activity decreased within the first 24 hours of life in both groups reflecting the depression of acute stress adaptation process triggered by the delivery. Therefore, EDA is a sensitive marker which is able to detect these subtle changes in sympathetic regulatory mechanisms.</p>
<p>Further, the elevation of NS.SCRs within the first postnatal day in all newborns indicates a physiological excitation of central nervous system. NS.SCRs as a discrete fluctuation of skin conductance around the baseline arise spontaneously, without the influence of an external stimuli and reflect states of increased “arousal” (<a ref-type="bibr" href="#j_acm-2023-0010_ref_014">14</a>). The increase of NS.SCRs within the first postnatal day may reflect changes related to an increased processing of perceptions and the activation of receptors in the context of adaptation to the extrauterine environment.</p>
<p>Lower NS.SCRs values in CS group during the immediate postnatal adaptation could be explained by the absence of physiological delivery mechanisms associated with stress response represented by the activation of SNS and stress hormones (<a ref-type="bibr" href="#j_acm-2023-0010_ref_010">10</a>). Another importnant factor contributing to the lower SNS activity is the general anesthesia of the mother during CS – an sympatholytic effect was described for sevoflurane and thiopental (<a ref-type="bibr" href="#j_acm-2023-0010_ref_015">15</a>, <a ref-type="bibr" href="#j_acm-2023-0010_ref_016">16</a>) – both drugs were used in our study. However, this effect seems to be temporary.</p>
<p>The precise understanding of SNS development in the earliest postnatal life is limited – there are no studies in the literature focusing on EDA measurements with regard to the mode of delivery in newborns so far. Therefore, our findings can provide novel insights into the SNS regulatory mechanisms immediately after birth and during the earliest postnatal life.</p>
</sec>
<sec id="j_acm-2023-0010_s_005"><div>CONCLUSION</div>
<p>Our study evaluated the effect of delivery mode on SNS measured by EDA in healthy term newborns within the first three postnatal days. The results revealed a lower <italic>“arousal”</italic> in CS group early after birth reflecting the absence of physiological labor mechanisms and the effect of general anesthesia on SNS leading to discrete early functional abnormalities in babies born by CS. Further research is required to confirm this finding.</p>
</sec>
</div>

Delivery Mode Affects the Sympathetic Nervous System in Healthy Term Newborns

Clinic of Neonatology, University Hospital and Jessenius Faculty of Medicine in Martin

Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin

Department of Physiology, Jessenius Faculty of Medicine in Martin

Acta Medica Martiniana

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

{"article-title":"Delivery Mode Affects the Sympathetic Nervous System in Healthy Term Newborns"}

Background
Spontaneous delivery represents an important way triggering the physiological mechanisms essential for a proper postnatal adaptation of a newborn....

Delivery Mode Affects the Sympathetic Nervous System in Healthy Term Newborns

Pubblicato online: 20 ago 2023

Pagine: 68 - 73

Ricevuto: 24 giu 2023

Accettato: 07 lug 2023

DOI: https://doi.org/10.2478/acm-2023-0010

Parole chiave
newborn, delivery mode, sympathetic nervous system, electrodermal activity

© 2023 Marek Kozar et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Delivery Mode Affects the Sympathetic Nervous System in Healthy Term Newborns

Pubblicato online: 20 ago 2023

Pagine: 68 - 73

Ricevuto: 24 giu 2023

Accettato: 07 lug 2023

DOI: https://doi.org/10.2478/acm-2023-0010

Parole chiavenewborn, delivery mode, sympathetic nervous system, electrodermal activity

© 2023 Marek Kozar et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Parole chiave
newborn, delivery mode, sympathetic nervous system, electrodermal activity